Developmental Changes in in Vitro Testosterone Production by Dispersed Leydig Cells During Fetal Life in Rats

Abstract

The age-related evolution during fetal days 18.5-21.5 of the capacity of collagenax-dispersed Leydig cells to produce testosterone and to respond to LH or dibutyryl cyclic AMP (dcAMP) was studied in vitro in the rat. When dispersed Leydig cells were incubated in control medium, testosterone secretion by cells from 18.5-day-old fetuses during the first 5 h was 100 and 50% higher than secretion by cells from 20.5-and 21.5-day-old fetuses, respectively. The secretion maximally stimulated by 100 ng/mL LH or stimulated by 1 mM dcAMP was also stronger on day 18.5 than on days 20.5 and 21.5 during the first 3 h of culture. The dose-response curves for LH showed that the ED50 was similar for day 18.5 and 20.5 cells (2 ng/mL LH). During the course of 24-h incubation, the secretion rates also changed with time and fetal age: Between 5 and 24 h of culture basal secretion decreased in day 18.5 cells, rose slightly in day 20.5 cells, and increased sharply in day 21.5 cells; in the same way, in the presence of LH or dcAMP, the secretion by day 18.5 cells decreased faster than that of day 20.5 or 21.5 cells. The basal testosterone secretion of the Leydig cells and its maximum steroidogenic capacity decrease during late fetal life in the rat, and there was no change in the sensitivity to LH during this period. The age-related differences in the variations of the secretion rates as a function of the duration of incubation suggest the existence of an evolution in extragonadotropic regulations during late fetal life.

In Utero and Lactational Exposures to Diethylhexyl-Phthalate Affect Two Populations of Leydig Cells in Male Long-Evans Rats1

“…Nipple retention and the increased frequencies of underdeveloped epididymides, testicular atrophy, hypospadias, and ectopic or absent testes were also seen in animals exposed to phthalates at 250 mg/kg per day or higher [36][37][38]. However, steroidogenic activity in FLCs peaks 1 to 2 days prior to birth on Day 19 of gestation [5]. The testosterone produced at this time is critical for male secondary sexual differentiation (i.e., development of the penis and sex accessory glands) [6].…”

“…Leydig cell marker cholesterol side-chain cleavage enzyme (P450scc) is detectable in rodents beginning on Gestational Day (GD) 12.5 in rodents. Fetal Leydig cells have maximal steroidogenic capacity on GD 19 [5] and secrete testosterone that is critical for inducing sexual development [6]. Fetal Leydig cells also play a critical role in the descent of the testis by synthesizing androgen and insulin-like growth factor 3 (INSL3) [7].…”

A new chapter in the bisphenol A story: bisphenol S and bisphenol F are not safe alternatives to this compound

“…3B). In the presence of 100 ng/mL LH, a concentration that induces the maximum steroidogenic response (78), the inhibitory effect of BPA in human testes was much less pronounced than in basal conditions. Indeed, only 10,000 nmol/L BPA (and not all the concentrations equal or up 10 nmol/L BPA as in basal conditions; Fig.…”

Rodent Leydig Cell Tumorigenesis: A Review of the Physiology, Pathology, Mechanisms, and Relevance to Humans

“…The adult rat testis typically contains 25 × 10 6 LCs so the fetal population would represent only 0.4% of the total number of LCs in the adult testis. Based on in vivo and in vitro data, testosterone production increases between gestation day 16 and 18, and then decreases until birth Weisz and Ward, 1980;Habert and Brignaschi, 1991). Because the steroidogenic capacity per fetal LC is markedly diminished by the end of fetal life, these LCs would contribute little to the total testosterone pool within the pubertal/adult testis.…”